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What’s ahead for pharmaceutical biotechnology ?
ELIZABETH M. TOPP, PH.D.DANE O. K I LDS IG CHA IR AND DEPARTMENT HEAD DEPARTMENT OF INDUSTR IAL AND PHYS ICAL PHARMACY PURDUE UNIVERS ITY
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BIRS/SQA Summit on Regulatory ExcellencePurdue University, West Lafayette, INMay 18‐19, 2017
Cell‐based therapiesAND DISTRIBUTED MANUFACTURING
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3http://www.diamond.ac.uk/Home/News/LatestFeatures/02_09_15.html
4http://www.sciwri.club/archives/3115
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cGMP
Autologous vs. Allogenic
Adapted from https://www.novartis.com
6Adapted from https://www.novartis.com
Local, distributed
cGMP manufacturing ?
Dispensing ?
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7https://www.ucl.ac.uk/pharmacy/pharmacy‐news/print‐medshttp://medshadow.org/news/fda‐warns‐against‐tablet‐splitting‐save‐money/
BiosimilarsAND ANALYTICAL RESOLUTION IN QA/QC
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http://fineartamerica.com/featured/herceptin‐breast‐cancer‐drug‐dr‐mark‐j‐winter.html
http://fineartamerica.com/featured/herceptin‐breast‐cancer‐drug‐dr‐mark‐j‐winter.html
10S. Kozlowski et al., NEJM, 365/5: 385‐388, 2011
AspirinMW = 180 g/mol
Monoclonal antibodyMW = 150,000 g/mol
833x larger
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A generic drug is identical…to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use…chemically identical to [the] branded counterpart…
www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm144456.htm
Biosimilars are…highly similar to an already FDA‐approved biological product, known as the biological reference product … [and have] no clinically meaningful differences from the reference product.
www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm241718.htm
How (bio)similar is (bio)similar enough?
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Not different
Different
• Low resolution analytical methods
• Small sample number (n)
• Higher resolution analytical methods
• Larger sample number (n)
A statistics issue?
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Which differences matter ?
Where do differences matter ?
Continuous ManufacturingAND THE MEANING OF “BATCH”
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http://www.pharmpro.com/articles/2011/08/continuous‐solid‐oral‐dosage‐processing
16http://xtalks.com/Continuous‐And‐Batch‐Manufacturing‐Pharmaceuticals.ashx
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Batch vs. continuousBATCH MANUFACTURING
Standard unit operations processing with limited process control
Off‐line testing after each unit operation and for final product
Regular cleaning and sterilization
Familiar
Regulatory acceptability
CONTINU0US MANUFACTURING
Smaller equipment and facilities, reduced capital cost
Process efficiency
Process flexibility
Shorter processing time
Reduced manual handling
In‐line monitoring
Closed loop process control
Real‐time release testing of finished product
17https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm341197.pdf
What’s a batch?
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21 CFR 210.3
Batch: a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture
Lot: a batch, or a specific identified portion of a batch, having uniform character and quality within specified limits; or, in the case of a drug product produced by continuous process, it is a specific identified amount produced in a unit of time or quantity
https://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm341197.pdf
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19http://www.nicomac.com/granulation.html
20https://commons.wikimedia.org/wiki/File:Lyophilization_of_Pharmaceuticals_in_Vial.JPG
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Keeping UpRESOURCES FOR YOUR ONGOING LEARNING
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22https://www.coursereport.com/resources/coding‐bootcamp‐vs‐college
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Colleges and academic units
Biotechnology Innovation and Regulatory Science
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$70 M federal$129 M state, industryTechnology innovationWorkforce development
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Re‐cap Cell‐based therapies and distributed manufacturing
Biosimilars and analytical resolution
Continuous manufacturing and the meaning of “batch”
Keeping up and new types of education
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